TIME DEPENDENCE OF Na-NITROPRUSSIDE ADMINISTRATION IN THE PREVENTION OF NEUTROPHIL INFILTRATION IN THE RAT ISCHEMIC KIDNEY1

Abstract

The aim of this study was to determine the ideal time of administration of Na-nitroprusside to prevent neutrophil infiltration in ischemically damaged kidneys. Sprague-Dawley rats were subjected to 75 min of renal warm ischemia and contralateral nephrectomy. The animals were divided into 7 groups: the ischemic control (IC), which received normal saline, the sham group without warm ischemia and the experimental groups, which received intravenous Na-nitroprusside (NP) (5 mg/kg) at 75, 30, 15, and 5 min prior to reperfusion. Another experimental group was given verapamil (V) (5 mg/kg) as a NO-independent vasodilator 5 min prior to reperfusion. The final evaluation included survival at seven days, serum creatinine (SCr) and blood urea nitrogen (BUN) daily for 3 days, and neutrophil infiltration determined by the presence of myeloperoxidase (MPO) in renal tissue at 2 hr after reperfusion. Histological damage was assessed at 24 hr. There were significant improvements in all parameters when the Na-NP was administered at 75, 30, and 15 min prior to reperfusion when compared with the control group (p < 0.05). There were no differences either in survival or renal function when the 5 min group was compared with the IC or V groups. It is concluded then, that Na-NP can be administered as late as 15 min before reperfusion and still have a protective effect. It appears that the mechanism of protection of Na-NP is due to blocking of one of the steps of the interaction between leukocytes and endothelium--migration. Furthermore, the verapamil (a NO-independent vasodilator) and Na-NP5 (a NO-dependent vasodilator) groups did not show a beneficial effect in these severely ischemically damaged kidneys, which might be one more reason to believe that Na-NP could be interacting at the level of leukocyte-endothelial cell interaction.